Since 1970, the death rate for coronary heart disease has declined dramatically, due in part to the success of aggressive interventional techniques such as coronary arterial bypass graft (CABG). However, since patency rates for CABG decrease dramatically after 10 years, many patients require a secondary procedure. Due to previous harvest or peripheral vascular disease progression, suitable autologous (self) vessels may not be available. Since synthetic grafts have not been used successfully for coronary- arterial reconstruction, there is no clinical alternative for CABG candidates lacking autologous vessels. Conservative estimates suggest 50,000 Americans die annually due to the lack of suitable graft material. Recently, we have reported a technique to produce functional blood vessels from a small skin biopsy. These human tissue engineered blood vessels (TEBVs) are fully autologous, fully biological, and capable of withstanding 20-fold physiological blood pressure. The vessels are suturable and have been implanted successfully in animals. The objective of this research plan is to expedite the commercial availability of clinically relevant TEBVs (20 cm in length and 4-6 mm in diameter). Specifically, we will develop a bioreactor to automate critical steps in the fabrication process. Histological and mechanical properties of the TEBVs will be examined to optimize and validate this process. PROPOSED COMMERCIAL APPLICATIONS: The initial target market is critical CABG patients with no suitable graft donor sites and stenoses untreatable with PCTA or stents. Conservative estimates suggest the U.S. market is currently 50,000 candidate patients per year and growing exponentially. TEBVs may also fulfill the imperative clinical need for small diameter vessels for bypass in the peripheral circulation. The sheet based technology used for this project may provide a platform for other tissue engineering applications, including A-V shunts for dialysis, tendons, ligaments, heart valves, and three dimensional tissues with a built in capillary network.